Pokemon (FBI-1) interacts with Smad4 to repress TGF-β-induced transcriptional responses

• Published in: Biochimica et biophysica acta 2015-03, Vol.1849 (3), p.270-281
• Main Authors: Yang, Yutao, Cui, Jiajun, Xue, Feng, Zhang, Chuanfu, Mei, Zhu, Wang, Yue, Bi, Mingjun, Shan, Dapeng, Meredith, Alex, Li, Hui, Xu, Zhi-Qing David
• Format: Article
• Language: English
• Subjects: Binding Sites; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Hep G2 Cells; Humans; Interaction; Pokemon; Protein Interaction Maps - genetics; Signal Transduction - genetics; Smad2 Protein - genetics; Smad2 Protein - metabolism; Smad3 Protein - genetics; Smad3 Protein - metabolism; Smad4; Smad4 Protein - genetics; Smad4 Protein - metabolism; TGF-β pathway; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptional Activation - genetics; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta - pharmacology
• ISSN: 1874-9399; 0006-3002; 1876-4320
• DOI: 10.1016/j.bbagrm.2014.12.008

Pokemon, an important proto-oncoprotein, is a transcriptional repressor that belongs to the POK (POZ and Krüppel) family. Smad4, a key component of TGF-β pathway, plays an essential role in TGF-β-induced transcriptional responses. In this study, we show that Pokemon can interact directly with Smad4 both in vitro and in vivo. Overexpression of Pokemon decreases TGF-β-induced transcriptional activities, whereas knockdown of Pokemon increases these activities. Interestingly, Pokemon does not affect activation of Smad2/3, formation of Smads complex, or DNA binding activity of Smad4. TGF-β1 treatment increases the interaction between Pokemon and Smad4, and also enhances the recruitment of Pokemon to Smad4-DNA complex. In addition, we also find that Pokemon recruits HDAC1 to Smad4 complex but decreases the interaction between Smad4 and p300/CBP. Taken together, all these data suggest that Pokemon is a new partner of Smad4 and plays a negative role in TGF-β pathway. •Pokemon interacts with Smad4 both in vitro and in vivo.•Pokemon represses TGF-β-induced transcriptional activities.•Pokemon influences the recruitment of transcriptional co-regulators to Smad4.